Search results for: oral cavity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1452

Search results for: oral cavity

612 CFD Simulation of the Pressure Distribution in the Upper Airway of an Obstructive Sleep Apnea Patient

Authors: Christina Hagen, Pragathi Kamale Gurmurthy, Thorsten M. Buzug

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CFD simulations are performed in the upper airway of a patient suffering from obstructive sleep apnea (OSA) that is a sleep related breathing disorder characterized by repetitive partial or complete closures of the upper airways. The simulations are aimed at getting a better understanding of the pathophysiological flow patterns in an OSA patient. The simulation is compared to medical data of a sleep endoscopic examination under sedation. A digital model consisting of surface triangles of the upper airway is extracted from the MR images by a region growing segmentation process and is followed by a careful manual refinement. The computational domain includes the nasal cavity with the nostrils as the inlet areas and the pharyngeal volume with an outlet underneath the larynx. At the nostrils a flat inflow velocity profile is prescribed by choosing the velocity such that a volume flow rate of 150 ml/s is reached. Behind the larynx at the outlet a pressure of -10 Pa is prescribed. The stationary incompressible Navier-Stokes equations are numerically solved using finite elements. A grid convergence study has been performed. The results show an amplification of the maximal velocity of about 2.5 times the inlet velocity at a constriction of the pharyngeal volume in the area of the tongue. It is the same region that also shows the highest pressure drop from about 5 Pa. This is in agreement with the sleep endoscopic examinations of the same patient under sedation showing complete contractions in the area of the tongue. CFD simulations can become a useful tool in the diagnosis and therapy of obstructive sleep apnea by giving insight into the patient’s individual fluid dynamical situation in the upper airways giving a better understanding of the disease where experimental measurements are not feasible. Within this study, it could been shown on one hand that constriction areas within the upper airway lead to a significant pressure drop and on the other hand a good agreement of the area of pressure drop and the area of contraction could be shown.

Keywords: biomedical engineering, obstructive sleep apnea, pharynx, upper airways

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611 Ezra Pound and James Joyce: Two Different Approaches to the Relation between Literature and Visual Arts

Authors: Espen Gronlie

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This paper will suggest that Ezra Pound and James Joyce are paradigmatic for two different approaches to literature and visual arts. Both authors are infamous for being difficult, but this does not mean that their works are similar. Pound famously promoted Joyce’s Ulysses and was instrumental in getting the work published in literary reviews. However, Pound did not appreciate Joyce’s artistic development in his so-called Work in Progress, which was published in 1939 under the title Finnegans Wake. Pound and Joyce will be read as representing two different approaches to literature and other forms of art. Pound can be seen as essentially influenced by cubism and modernist techniques such as collage and montage. While many critics have used these notions to describe The Cantos, this paper will suggest reading Pound’s opus magnum in relation to Finnegans Wake. The latter work shows how Joyce remained tied to an idea of the literary work as sound, as something which may – or perhaps even should – be read aloud. In contrast, Pound’s The Cantos show clear signs of being influenced by experiments in the visual arts. The paper will argue that Pound intended to develop his work in order to bring literature 'up to date' with the development in visual arts, while Joyce stuck to a more classical understanding of the literary work as composed for oral presentation.

Keywords: collage, conceptualism, montage, literature and visual arts

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610 Uranoplasty Using Tongue Flap for Bilateral Clefts

Authors: Saidasanov Saidazal Shokhmurodovich, Topolnickiy Orest Zinovyevich, Afaunova Olga Arturovna

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Relevance: Bilateral congenital cleft is one of the most complex forms of all clefts, which makes it difficult to choose a surgical method of treatment. During primary operations to close the hard and soft palate, there is a shortage of soft tissues and their lack during standard uranoplasty, and these factors aggravate the period of rehabilitation of patients. Materials and methods: The results of surgical treatment of children with bilateral cleft, who underwent uranoplasty using a flap from the tongue, were analyzed. The study used methods: clinical and statistical, which allowed us to solve the tasks, based on the principles of evidence-based medicine. Results and discussion: in our study, 15 patients were studied, who underwent surgical treatment in the following volume: uranoplasty using a flap from the tongue in two stages. Of these, 9 boys and 6 girls aged 2.5 to 6 years. The first stage was surgical treatment in the volume: veloplasty. The second stage was a surgical intervention in volume: uranoplasty using a flap from the tongue. In all patients, the width of the cleft ranged from 1.6-2.8 cm. All patients in this group were orthodontically prepared. Using this method, the surgeon can achieve the following results: maximum narrowing of the palatopharyngeal ring, long soft palate, complete closure of the hard palate, alveolar process, and the mucous membrane of the nasal cavity is also sutured, which creates good conditions for the next stage of osteoplastic surgery. Based on the result obtained, patients have positive results of working with a speech therapist. In all patients, the dynamics were positive without complications. Conclusions: Based on our observation, tongue flap uranoplasty is one of the effective techniques for patients with wide clefts of the hard and soft palate. The use of a flap from the tongue makes it possible to reduce the number of repeated reoperations and improve the quality of social adaptation of this group of patients, which is one of the important stages of rehabilitation. Upon completion of the stages of rehabilitation, all patients had the maximum improvement in functional, anatomical and social indicators.

Keywords: congenital cleft lips and palate, bilateral cleft, child surgery, maxillofacial surgery

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609 Environmental Conditions Simulation Device for Evaluating Fungal Growth on Wooden Surfaces

Authors: Riccardo Cacciotti, Jiri Frankl, Benjamin Wolf, Michael Machacek

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Moisture fluctuations govern the occurrence of fungi-related problems in buildings, which may impose significant health risks for users and even lead to structural failures. Several numerical engineering models attempt to capture the complexity of mold growth on building materials. From real life observations, in cases with suppressed daily variations of boundary conditions, e.g. in crawlspaces, mold growth model predictions well correspond with the observed mold growth. On the other hand, in cases with substantial diurnal variations of boundary conditions, e.g. in the ventilated cavity of a cold flat roof, mold growth predicted by the models is significantly overestimated. This study, founded by the Grant Agency of the Czech Republic (GAČR 20-12941S), aims at gaining a better understanding of mold growth behavior on solid wood, under varying boundary conditions. In particular, the experimental investigation focuses on the response of mold to changing conditions in the boundary layer and its influence on heat and moisture transfer across the surface. The main results include the design and construction at the facilities of ITAM (Prague, Czech Republic) of an innovative device allowing for the simulation of changing environmental conditions in buildings. It consists of a square section closed circuit with rough dimensions 200 × 180 cm and cross section roughly 30 × 30 cm. The circuit is thermally insulated and equipped with an electric fan to control air flow inside the tunnel, a heat and humidity exchange unit to control the internal RH and variations in temperature. Several measuring points, including an anemometer, temperature and humidity sensor, a loading cell in the test section for recording mass changes, are provided to monitor the variations of parameters during the experiments. The research is ongoing and it is expected to provide the final results of the experimental investigation at the end of 2022.

Keywords: moisture, mold growth, testing, wood

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608 Effects of Delphinidin on Lipid Metabolism in HepG2 Cells and Diet-Induced Obese Mice

Authors: Marcela Parra-Vargas, Ana Sandoval-Rodriguez, Roberto Rodriguez-Echevarria, Jose Dominguez-Rosales, Juan Armendariz-Borunda

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Non-alcoholic fatty liver disease (NAFLD) is characterized by an excess of hepatic lipids, and it is to author’s best knowledge, the most prevalent chronic liver disorder. Anthocyanin-rich food consumption is linked to health benefits in metabolic disorders associated with obesity and NAFLD, although the precise functional role of anthocyanidin delphinidin (Dp) has yet to be established. The aim of this study was to investigate the effect of the Dp in NAFLD metabolic alterations by evaluating prevention or amelioration of hepatic lipid accumulation, as well as molecular mechanisms in two experimental obesity-related models of NALFD. In vitro: HepG2 cells were incubated with sodium palmitate (PA, 1 mM) to induce lipotoxic damage, and concomitantly treated with Dp (180 uM) for 24 h. Subsequently, total lipid accumulation was measured by colorimetric staining with Oil Red O, and total intrahepatic triglycerides were determined by an enzymatic assay. To assess molecular mechanisms, cells were pre-treated with PA for 24 h and then exposed to Dp for 1 h. In vivo: four-week-old male C57BL/6Nhsd mice were allocated in two main groups. Mice were fed with standard diet (control) or high-fat and high-carbohydrate diet (45% fat, HFD) for 16 wk to induce NAFLD. Then HFD was divided into subgroups: one treated orally with Dp (15 mg/kg bw, HFD-Dp) every day for 4 wk, while HFD group treated with vehicle (DMSO). Weight and fasting glucose were recorded weekly, while dietary ingestion was measured daily. Insulin tolerance test was performed at the end of treatment. Liver histology was evaluated with H&E and Masson’s trichrome stain. RT-PCR was used to evaluate gene expression and Western Blot to determine levels of protein in both experimental models. Parametric data were analyzed with one-way ANOVA and Tukey’s post-hoc test. Kruskal-Wallis and Mann-Whitney U test for non-parametric data, and P < 0.5 were considered significant. Dp prevented hepatic lipid accumulation by PA in HepG2 hepatocytes. Furthermore, Dp down-regulated gene expression of SREBP1c, FAS, and CPT1a without modifying AMPK phosphorylation levels. In vivo, Dp oral administration did not ameliorate lipid metabolic alterations raised by HFD. Adiposity, dietary ingestion, fasting glucose, and insulin sensitivity after Dp treatment remained similar to HFD group. Histological analysis showed hepatic damage in HFD groups and no differences between HFD and HFD-Dp groups were found. Hepatic gene expression of ACC and FAS were not altered by HFD. SREBP1c was similar in both HFD and HFD-Dp groups. No significant changes were observed in SREBP1c, ACC, and FAS adipose tissue gene expression by HFD or Dp treatment. Additionally, immunoblotting analysis revealed no changes in pathway SIRT1-LKB-AMPK and PPAR alpha by both HFD groups compared to control. In conclusion, the antioxidant Dp may provoke beneficial effects in the prevention of hepatic lipid accumulation. Nevertheless, the oral dose administrated in mice that simulated the total intake of anthocyanins consumed daily by humans has no effect as a treatment on hepatic lipid metabolic alterations and histological abnormalities associated with exposure to chronic HFD. A healthy lifestyle with regular intake of antioxidants such as anthocyanins may prevent metabolic alterations in NAFLD.

Keywords: anthocyanins, antioxidants, delphinidin, non-alcoholic fatty liver disease, obesity

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607 Understanding Health-Related Properties of Grapes by Pharmacokinetic Modelling of Intestinal Absorption

Authors: Sophie N. Selby-Pham, Yudie Wang, Louise Bennett

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Consumption of grapes promotes health and reduces the risk of chronic diseases due to the action of grape phytochemicals in regulation of Oxidative Stress and Inflammation (OSI). The bioefficacy of phytochemicals depends on their absorption in the human body. The time required for phytochemicals to achieve maximal plasma concentration (Tₘₐₓ) after oral intake reflects the time window of maximal bioefficacy of phytochemicals, with Tₘₐₓ dependent on physicochemical properties of phytochemicals. This research collated physicochemical properties of grape phytochemicals from white and red grapes to predict their Tₘₐₓ using pharmacokinetic modelling. The predicted values of Tₘₐₓ were then compared to the measured Tₘₐₓ collected from clinical studies to determine the accuracy of prediction. In both liquid and solid intake forms, white grapes exhibit a shorter Tₘₐₓ range (0.5-2.5 h) versus red grapes (1.5-5h). The prediction accuracy of Tₘₐₓ for grape phytochemicals was 33.3% total error of prediction compared to the mean, indicating high prediction accuracy. Pharmacokinetic modelling allows prediction of Tₘₐₓ without costly clinical trials, informing dosing frequency for sustained presence of phytochemicals in the body to optimize the health benefits of phytochemicals.

Keywords: absorption kinetics, phytochemical, phytochemical absorption prediction model, Vitis vinifera

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606 The Theory of Domination at the Bane of Conflict Resolution and Peace Building Processes in Cameroon

Authors: Nkatow Mafany Christian

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According to UNHCR’s annual Database, humanitarian crises have globally been on the increase since the beginning of the 21st Century, especially in the Middle East and in Sub-Saharan Africa. Cameroon is one of the countries that has suffered tremendously from humanitarian challenges in recent years, especially with crises in the Far North, the East and its Two English-speaking Regions. These have been a result of failed mechanisms in conflict resolution peacebuilding by the government. The paper draws from this basic premise to argue that the failure to reach a consensus in order to curb internal conflicts has largely been due to the government’s attachment to the domineering attitude which emphasizes an imposition of peace terms by a superordinate (government) agency on the subordinate (aggrieved) entities. This has stalled peace efforts that have so far been engaged to address the dreaded armed conflicts in the North and South West Regions, leading to the persistence of the armed conflict. The paper exploits written, oral and online sources to sustain its argument. It suggests that an eclectic approach to resolving conflicts, which emphasizes open and frank dialogue as well as a review of the root causes, can go a long way not only to build trust but also to address the Anglophone-Cameroonian problems in Cameroon.

Keywords: conflict, conflict resolution, peace building, humanitarian crisis

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605 Prevalence of Iron Deficiency Anaemia and Its Impact on Nutritional Status of Rural Pregnant Women

Authors: Nuzhat Sultana

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Iron deficiency (IDA) is the commonest nutritional anemia present in Indian pregnant women. The overall development of a fetus is determined to a great extent by the type of nourishment mother receives right from its conception. To study the risk factors of iron deficiency anemia, two hundred rural pregnant women in the age of 15-35 years in the second trimester of pregnancy from the countryside of Beed district was selected. These samples were divided into groups 'A' (experimental samples) and 'C' (control samples). Experimental samples were received oral supplementation of iron and folic acid for ninety days, but control samples did not receive any supplementation. All the samples were observed anthropometrically, biochemically and clinically before and after supplementation. The study result shows that maximum numbers of i.e. 75% pregnant women had low levels of weight and hemoglobin as compared to standard weight and HB level. However, after supplementation only in experimental group weight and HB level was increased. It was observed that prevalence of risk factors associated with anemia was higher in rural pregnant women. Poverty, illiteracy, faulty food habits, and poor intake of iron during pregnancy are the main causative factors for iron deficiency anemia in rural pregnant women.

Keywords: iron deficiency, anemia, risk factors, pregnancy

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604 The Rendering of Sex-Related Expressions by Court Interpreters in Hong Kong: A Corpus-Based Approach

Authors: Yee Yan Crystal Kwong

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The essence of rape is the absence of consent to sexual intercourse. Yet, the definition of consent is not absolute and allows for subjectivity. In this case, the accuracy of oral interpretation becomes very important as the narratives of events and situation, as well as the register and style of speakers would influence the juror decision making. This paper first adopts a corpus-based approach to investigate how court interpreters in Hong Kong handle expressions that refer to sexual activities. The data of this study will be based on online corpus :From legislation to translation, from translation to interpretation: The narrative of sexual offences. The corpus comprises the transcription of five separate rape trials and all of these trials were heard with the presence of an interpreter. Since there are plenty of sex-related expressions used by witnesses and defendants in the five cases, emphasis will be put on those which have an impact on the definition of rape. With an in-depth analysis of the interpreted utterances, different interpreting approaches will be identified to observe how interpreters retain the intended meanings. Interviews with experienced court interpreters will also be conducted to revisit the validity of the traditional verbatim standard. At the end of this research, various interpreting approaches will be compared and evaluated. A redefinition of interpreters' institutional role, as well as recommendations for interpreting learners will be provided.

Keywords: court interpreting, interpreters, legal translation, slangs

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603 Viscous Flow Computations for the Diffuser Section of a Large Cavitation Tunnel

Authors: Ahmet Y. Gurkan, Cagatay S. Koksal, Cagri Aydin, U. Oral Unal

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The present paper covers the viscous flow computations for the asymmetric diffuser section of a large, high-speed cavitation tunnel which will be constructed in Istanbul Technical University. The analyses were carried out by using the incompressible Reynold-Averaged-Navier-Stokes equations. While determining the diffuser geometry, a high quality, separation-free flow field with minimum energy loses was particularly aimed. The expansion angle has a critical role on the diffuser hydrodynamic performance. In order obtain a relatively short diffuser length, due to the constructive limitations, and hydrodynamic energy effectiveness, three diffuser sections with varying expansion angles for side and bottom walls were considered. A systematic study was performed to determine the most effective diffuser configuration. The results revealed that the inlet condition of the diffuser greatly affects its flow field. The inclusion of the contraction section in the computations substantially modified the flow topology in the diffuser. The effect of the diffuser flow on the test section flow characteristics was clearly observed. The influence of the introduction of small chamfers at the corners of the diffuser geometry is also presented.

Keywords: asymmetric diffuser, diffuser design, cavitation tunnel, viscous flow, computational fluid dynamics (CFD), rans

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602 Investigation of Possible Precancerous Viral Markers in Dental Follicles of Asymptomatic Impacted Teeth

Authors: Serap Keskin Tunç, Cennet Neslihan Eroğlu, Sevinç Şahin, Selda Seçkin

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It has been suggested that various viruses may play a role in the pathogenesis of cancerous oral lesions in the literature. The aim of this study was to investigate the presence of both possible precancerous viral markers (HPV, HHV8, HSV1, HSV2, and EBV), and p53 and Ki-67 in the dental follicles of asymptomatic impacted teeth. A hundred healthy volunteers, older than 18 years old, included in the study. Dental follicles of extracted impacted teeth were excised and fixated in 10% formaldehyde. Histopathological and immunohistochemical examinations using HPV (containing HPV 8 and HPV 11), p16 (containing HPV 16), HHV8, HSV1, HSV2, EBV, p53 and Ki-67 antibodies were carried out. Also, the immunohistochemical results were correlated with the clinicopathological feature by Chi-square test statistically No dysplasia or neoplasm was observed. 62% of the cases were positive for p16, 32% were positive for EBV, 26% were positive for HSV1, immunohistochemically. All cases were immunonegative for HPV, HSV2, and HHV8. There was statistically significant correlation between overexpression of p53 with both EBV and p16 positivity (p<0.05). Direct correlation between higher expression of Ki-67 between EBV immunopositivity was detected (p<0.05). Thus, these viruses may be suggested to show trophism to the dental follicles acting as a reservoir. In conclusion, all dental follicles of extracted impacted teeth should be examined histopathologically in order to detect and prevent possible viral oncogenesis.

Keywords: dental follicles, Ki67, p53, precancerous markers viral markers

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601 Reduction of the Cellular Infectivity of SARS-CoV-2 by a Mucoadhesive Nasal Spray

Authors: Adam M. Pitz, Gillian L. Phillipson, Jayant E. Khanolkar, Andrew M. Middleton

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New emerging evidence suggests that the nose is the predominant route for entry of the SARS-CoV-2 virus into the host. A virucidal suspension test (conforming in principle to the European Standard EN14476) was conducted to determine whether a commercial liquid gel intranasal spray containing 1% of the mucoadhesive hydroxypropyl methylcellulose (HPMC) could inhibit the cellular infectivity of the SARS-CoV-2 coronavirus. Virus was added to the test product samples and to controls in a 1:8 ratio and mixed with one part bovine serum albumin as an interfering substance. The test samples were pre-equilibrated to 34 ± 2°C (representing the temperature of the nasopharynx) with the temperature maintained at 34 ± 2°C for virus contact times of 1, 5 and 10 minutes. Neutralized aliquots were inoculated onto host cells (Vero E6 cells, ATCC CRL-1586). The host cells were then incubated at 36 ± 2°C for a period of 7 days. The residual infectious virus in both test and controls was detected by viral-induced cytopathic effect. The 50% tissue culture infective dose per mL (TCID50/mL) was determined using the Spearman-Karber method with results reported as the reduction of the virus titer due to treatment with test product, expressed as log10. The controls confirmed the validity of the results with no cytotoxicity or viral interference observed in the neutralized test product samples. The HPMC formulation reduced SARS-CoV-2 titer, expressed as log10TCID50, by 2.30 ( ± 0.17), 2.60 ( ± 0.19), and 3.88 ( ± 0.19) with the respective contact times of 1, 5 and 10 minutes. The results demonstrate that this 1% HPMC gel formulation can reduce the cellular infectivity of the SARS-CoV-2 virus with an increasing viral inhibition observed with increasing exposure time. This 1% HMPC gel is well tolerated and can reside, when delivered via nasal spray, for up to one hour in the nasal cavity. We conclude that this intranasal gel spray with 1% HPMC repeat-dosed every few hours may offer an effective preventive or early intervention solution to limit the transmission and impact of the SARS-CoV-2 coronavirus.

Keywords: hydroxypropyl methylcellulose, mucoadhesive nasal spray, respiratory viruses, SARS-CoV-2

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600 Study of the Architectural Heritage and Culture of Bene Israeli Community in Raigad, Maharashtra

Authors: Nikita Mahajani

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The Bene Israel is the oldest Jewish community on the subcontinent, and their shipwreck off the coast of Navgaon (a coastal settlement south of Alibaug), in which only seven men and women survived, anticipated the first millennia of their residence in the Konkan. The community was cut off from mainstream Judaism for decades as a result of its poverty. Almost all of the Bene Israel people in the northern Konkan region have relocated to Israel. The few who remained have settled down in Mumbai and Thane. Despite this, they have left a rich cultural legacy, as seen by their houses, cemeteries and synagogues. Even though the population has reduced owing to outside migration, much of this built legacy has survived. This paper attempts to examine the Jewish architectural heritage in Raigad with an aim to recreate their cultural, social and economic history. Oral histories by interviews of the Bene Israel community from Revdanda helped gain information about naming customs, migrations, professions, religious customs and funeral practices. The findings of this research reveal that most synagogues in Raigad district are shut due to a lack of Bene Israelis coming for prayers. The cemeteries are in a dilapidated condition. The little-known Bene Israeli community of Raigad is a seamless blend of Maharashtrian and Jew culture and feels more homely in India.

Keywords: Konkan, Alibag, Revdanda, Pen, Bene Israeli, Indian jews, synagogue, cemetry

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599 Possibilities of Postmortem CT to Detection of Gas Accumulations in the Vessels of Dead Newborns with Congenital Sepsis

Authors: Uliana N. Tumanova, Viacheslav M. Lyapin, Vladimir G. Bychenko, Alexandr I. Shchegolev, Gennady T. Sukhikh

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It is well known that the gas formed as a result of postmortem decomposition of tissues can be detected already 24-48 hours after death. In addition, the conditions of keeping and storage of the corpse (temperature and humidity of the environment) significantly determine the rate of occurrence and development of posthumous changes. The presence of sepsis is accompanied by faster postmortem decomposition and decay of the organs and tissues of the body. The presence of gas in the vessels and cavities can be revealed fully at postmortem CT. Radiologists must certainly report on the detection of intraorganic or intravascular gas, wich was detected at postmortem CT, to forensic experts or pathologists before the autopsy. This gas can not be detected during autopsy, but it can be very important for establishing a diagnosis. To explore the possibility of postmortem CT for the evaluation of gas accumulations in the newborns' vessels, who died from congenital sepsis. Researched of 44 newborns bodies (25 male and 19 female sex, at the age from 6 hours to 27 days) after 6 - 12 hours of death. The bodies were stored in the refrigerator at a temperature of +4°C in the supine position. Grouped 12 bodies of newborns that died from congenital sepsis. The control group consisted of 32 bodies of newborns that died without signs of sepsis. Postmortem CT examination was performed at the GEMINI TF TOF16 device, before the autopsy. The localizations of gas accumulations in the vessels were determined on the CT tomograms. The sepsis diagnosis was on the basis of clinical and laboratory data and autopsy results. Gases in the vessels were detected in 33.3% of cases in the group with sepsis, and in the control group - in 34.4%. A group with sepsis most often the gas localized in the heart and liver vessels - 50% each, of observations number with the detected gas in the vessels. In the heart cavities, aorta and mesenteric vessels - 25% each. In control most often gas was detected in the liver (63.6%) and abdominal cavity (54.5%) vessels. In 45.5% the gas localized in the cavities, and in 36.4% in the vessels of the heart. In the cerebral vessels and in the aorta gas was detected in 27.3% and 9.1%, respectively. Postmortem CT has high diagnostic capabilities to detect free gas in vessels. Postmortem changes in newborns that died from sepsis do not affect intravascular gas production within 6-12 hours. Radiation methods should be used as a supplement to the autopsy, including as a kind of ‘guide’, with the indication to the forensic medical expert of certain changes identified during CT studies, for better definition of pathological processes during the autopsy. Postmortem CT can be recommend as a first stage of autopsy.

Keywords: congenital sepsis, gas, newborn, postmortem CT

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598 Botulinum A Toxin Injection in Two Filipino Brothers with X-linked Dystonia-Parkinsonism (XDP) in Cebu City, Philippines: A Case Report

Authors: Ana Katrina C. Longos, Jarungchai Anton S. Vatanagul

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Objectives: To present a case of two Filipino male siblings initially seen with parkinsonism and eventually with dystonia and to present botulinum A toxin as part of the treatment for X-linked dystonia parkinsonism in Cebu City. Discussion: A 54 year old man presented initially with parkinsonian symptoms and later developed oromandibular and truncal dystonia. Further history revealed that he had an older brother who also presented with the same symptoms. Neuroimaging done on both patients revealed CVD infarcts in the pons and corona radiata respectively which where were not compatible with their symptoms. Family history revealed that their mother was originally from Panay and a diagnosis of X-linked dystonia parkinsonism (XDP) was made. Both patients were able to receive botulinum A toxin injections which provided temporary relief of symptoms. Conclusion: XDP was considered in 2 Filipino male siblings who presented with oromandibular dystonia, truncal dystonia, shuffling gait, resting tremors with ancestry from Panay on the maternal side. There is no cure for XDP, only symptomatic treatment. Until recently, only oral chemotherapy was available in Cebu. Botulinum A toxin injection done in both patients afforded temporary resolution of symptoms.

Keywords: XDP, dystonia of Panay, lubag, dystonia parkinsonism, botulinum a toxin

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597 Curcumin and Methotrexate Loaded Montmollilite Clay for Sustained Oral Drug Delivery Application

Authors: Subrata Kar, Banani Kundu, Papiya Nandy, Ruma Basu, Sukhen Das

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Natural montmorilollite clay is a common ingredient in pharmaceutical products, both as excipients and active support; hence considered as suitable candidate for Drug Delivery System. In this work, cationic detergent CTAB is used to increase the interlayer spacing of Na+-Montmoriollite clay to intercalate curcumin and methotrexate. Methotrexate is a folic acid antagonist, anti-proliferative and immunosuppressive agent; while curcumin is a bioactive constituent of rhizomes of Curcuma longa, possessing remarkable chemo-preventive and anti-inflammatory properties. The resultant inorganic-organic hybrids are characterized by X-ray diffraction (XRD), Infrared spectroscopy (FTIR) and Thermo Gravimetric Analysis (TGA) to confirm successful intercalation of curcumin and Methotrexate within clay layers. Pharmaceutical investigation of the hybrids is explored by studying the drug loading (%), encapsulation efficiency and release kinetics. Finally in-vitro studies are performed using cancer cells to find the effect of released curcumin to improve the sensitivity of clay bound methotrexate to ameliorate cell death compared to their effectiveness when used without the inorganic aluminosilicate vehicle.

Keywords: montmorillonite, methotrexate, curcumin, loading efficiency, release kinetics, anticancer activity

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596 Human-Computer Interaction Pluriversal Framework for Ancestral Medicine App in Bogota: Asset-Based Design Case Study

Authors: Laura Niño Cáceres, Daisy Yoo, Caroline Hummels

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COVID-19 accelerated digital healthcare technology usage in many countries, such as Colombia, whose digital healthcare vision and projects are proof of this. However, with a significant cultural indigenous and Afro-Colombian heritage, only some parts of the country are willing to follow the proposed digital Western approach to health. Our paper presents the national healthcare system’s digital narrative, which we contrast with the micro-narrative of an Afro-Colombian ethnomedicine unit in Bogota called Kilombo Yumma. This ethnomedical unit is building its mobile app to safeguard and represent its ancestral medicine practices in local and national healthcare information systems. Kilombo Yumma is keen on promoting their beliefs and practices, which have been passed on through oral traditions and currently exist in the hands of a few older women. We unraveled their ambition, core beliefs, and practices through asset-based design. These assets outlined pluriversal and decolonizing forms of digital healthcare to increase social justice and connect Western and ancestral medicine digital opportunities through HCI.

Keywords: asset-based design, mobile app, decolonizing HCI, Afro-Colombian ancestral medicine

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595 Tuberculosis in Humans and Animals in the Eastern Part of the Sudan

Authors: Yassir Adam Shuaib, Stefan Niemann, Eltahir Awad Khalil, Ulrich Schaible, Lothar Heinz Wieler, Mohammed Ahmed Bakhiet, Abbashar Osman Mohammed, Mohamed Abdelsalam Abdalla, Elvira Richter

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Tuberculosis (TB) is a chronic bacterial disease of humans and animals and it is characterized by the progressive development of specific granulomatous tubercle lesions in affected tissues. In a six-month study, from June to November 2014, a total of 2,304 carcasses of cattle, camel, sheep, and goats slaughtered at East and West Gaash slaughterhouses, Kassala, were investigated during postmortem, in parallel, 101 sputum samples from TB suspected patients at Kassala and El-Gadarif Teaching Hospitals were collected in order to investigate tuberculosis in animals and humans. Only 0.1% carcasses were found with suspected TB lesions in the liver and lung and peritoneal cavity of two sheep and no tuberculous lesions were found in the carcasses of cattle, goats or camels. All samples, tissue lesions and sputum, were decontaminated by the NALC-NaOH method and cultured for mycobacterial growth at the NRZ for Mycobacteria, Research Center Borstel, Germany. Genotyping and molecular characterization of the grown strains were done by line probe assay (GenoType CM and MTBC) and 16S rDNA, rpoB gene, and ITS sequencing, spoligotyping, MIRU-VNTR typing and next generation sequencing (NGS). Culture of the specimens revealed growth of organisms from 81.6% of all samples. Mycobacterium tuberculosis (76.2%), M. intracellulare (14.2%), mixed infection with M. tuberculosis and M. intracellulare (6.0%) and mixed infection with M. tuberculosis and M. fortuitum and with M. intracellulare and unknown species (1.2%) were detected in the sputum samples and unknown species (1.2%) were detected in the samples of one of the animals tissues. From the 69 M. tuberculosis strains, 25 (36.2%) were showing either mono-drug-resistant or multi-drug-resistant or poly-drug-resistant but none was extensively drug-resistant. In conclusion, the prevalence of TB in animals was very low while in humans M. tuberculosis-Delhi/CAS lineage was responsible for most cases and there was an evidence of MDR transmission and acquisition.

Keywords: animal, human, slaughterhouse, Sudan, tuberculosis

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594 Data Analysis for Taxonomy Prediction and Annotation of 16S rRNA Gene Sequences from Metagenome Data

Authors: Suchithra V., Shreedhanya, Kavya Menon, Vidya Niranjan

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Skin metagenomics has a wide range of applications with direct relevance to the health of the organism. It gives us insight to the diverse community of microorganisms (the microbiome) harbored on the skin. In the recent years, it has become increasingly apparent that the interaction between skin microbiome and the human body plays a prominent role in immune system development, cancer development, disease pathology, and many other biological implications. Next Generation Sequencing has led to faster and better understanding of environmental organisms and their mutual interactions. This project is studying the human skin microbiome of different individuals having varied skin conditions. Bacterial 16S rRNA data of skin microbiome is downloaded from SRA toolkit provided by NCBI to perform metagenomics analysis. Twelve samples are selected with two controls, and 3 different categories, i.e., sex (male/female), skin type (moist/intermittently moist/sebaceous) and occlusion (occluded/intermittently occluded/exposed). Quality of the data is increased using Cutadapt, and its analysis is done using FastQC. USearch, a tool used to analyze an NGS data, provides a suitable platform to obtain taxonomy classification and abundance of bacteria from the metagenome data. The statistical tool used for analyzing the USearch result is METAGENassist. The results revealed that the top three abundant organisms found were: Prevotella, Corynebacterium, and Anaerococcus. Prevotella is known to be an infectious bacterium found on wound, tooth cavity, etc. Corynebacterium and Anaerococcus are opportunist bacteria responsible for skin odor. This result infers that Prevotella thrives easily in sebaceous skin conditions. Therefore it is better to undergo intermittently occluded treatment such as applying ointments, creams, etc. to treat wound for sebaceous skin type. Exposing the wound should be avoided as it leads to an increase in Prevotella abundance. Moist skin type individuals can opt for occluded or intermittently occluded treatment as they have shown to decrease the abundance of bacteria during treatment.

Keywords: bacterial 16S rRNA , next generation sequencing, skin metagenomics, skin microbiome, taxonomy

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593 Case Report: Clinical Improvement of Forbrain Neurologic Signs in 3- Month- Old Persian Mastiff Dog with Calvarial Hyperostosis Syndrome after Corticosteroid, Antiepileptic and Antibiotic Therapy

Authors: Hamidreza Jahani, Zahra Salehzadeh, Ehsan Amini, Mohsen Tohidifar

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Calvarial Hyperostosis Syndrome (CHS) is a benign bone disease of the skull. It is a non-neoplastic and proliferative bone disease, and the main feature of the disease is progressive and asymmetrical bone involvement. CHS is mostly reported in young male and female bullmastiff dogs and less frequently in other breeds. The etiology of CHS is unknown. This is the first case report of CHS in Iran. A 3-month-old male Persian Mastiff was presented with chief complaints of multiple episodes of seizure, pacing, bizarre behavior, delayed growth, head pressing, and difficulty in opening the mouth. Central blindness and open fontanelles were observed in clinical examination. No abnormality was found in the complete blood count and routine blood biochemical tests. CT scan findings include cortical thickening of frontal and parietal bones and enlargement of the left retropharyngeal lymph node. For treatment, oral clindamycin for two weeks, prednisolone and phenobarbital for one month, respectively, were administrated, and the case showed improvement after a week and recovered after one month.

Keywords: calvarial hyperostosis, Persian Mastiff, frontal bone, seizure

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592 An Investigation of Anticancer Fluorinated Aza-Heterocycles

Authors: Darya O. Prima, Elena V. Vorontsova, Yuri G. Slizhov, Andrey V. Zibarev

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A broad family of carbocycle-fluorinated aza-heterocycles including 1,3-benzodiazoles (benzimidazoles), 1,2,3-benzotriazoles, 2,1,3-benzothia/selenadiazoles and 1,4-benzodiazines (quinoxalines) was synthesized in the unified way and assessed for cytotoxicity towards the Hep2 (laryngeal epidermoid carcinoma, a kind of oral cancer) cells. The diazoles, triazoles and selenadiazoles revealed low medium inhibitory concentrations IC50 = 2.2-26.4 µМ and induced the cells’ apoptosis at low concentrations C = 1-25 µМ. For selenadiazoles, cell death dynamics was observed already in the first hours after the treatment. Replacement of one atom F by group Me2N in some cases enlarged apoptotic activity of the compounds towards the Hep2 cells. In contrast, the archetypal (i.e. non-fluorinated) 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole were low toxic (IC50 > 100 µM) and induced apoptosis only at high concentrations. The chlorinated congeners of the heterocycles under discussion were highly toxic towards the Hep2 cells but revealed insignificant ability to induce their apoptosis. Overall, the findings above suggest that fluorinated 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole derivatives can be considered as potential anticancer drugs. For the laryngeal epidermoid carcinoma (for which, according to available statistics, the five-year survival rate remained ~50% during the past 30 years), it is especially important since surgical treatment is seriously complicated here thus encouraging medicament one.

Keywords: Apoptosis, aza-heterocycles, cytotoxicity, fluorinated, Hep2 cells, synthesis

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591 Prevalence of Menopausal Women with Clinical Symptoms of Allergy and Evaluation the Effect of Sex Hormone Combined with Anti-Allergy Treatment

Authors: Yang Wei, Xueyan Wang, Hui Zou

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Objective: Investigation the prevalence of menopausal symptoms in patients with allergic symptoms, evaluation of the effect of sex hormones combined with anti-allergic therapy in these patients. Method: Age of 45-65 years old women with allergic symptoms at the same time in gynecological-endocrinology clinic in our hospital were selected from Feb 1 to May 31, 2010, randomly. The patients were given oral estradiol valerate plus progestin pills combined with anti-allergy treatment and then evaluated twice a week and one month later. Evaluation criterion: Menopause Rating Scale (MRS) and the degree of clinical symptoms were used to evaluate menopause and allergy separately. Results: 1) There were 195 cases of patients with menopausal symptoms at the age. Their MRS were all over 15. 2) Among them 45 patients were with allergic symptom accounted for 23% which were diagnosed by allergic department. 3) Evaluated after one week: the menopausal symptoms were improved and MRS were less than or equal to 5 in all these patients; the skin symptom of allergic symptoms vanished completely. 4) Evaluated after one month: Menopause symptoms were improved steadily; other clinical symptoms of allergy were also improved or without recurrence. Conclusion: The incidence rate of menopausal women with clinical symptoms of allergic diseases is high and it needs attention. The effect of sex hormones combined with anti-allergic therapy is obvious.

Keywords: menopausal, allergy, sex hormone, anti-allergy treatment

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590 The Role of QX-314 and Capsaicin in Producing Long-Lasting Local Anesthesia in the Animal Model of Trigeminal Neuralgia

Authors: Ezzati Givi M., Ezzatigivi N., Eimani H.

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Trigeminal Neuralgia (TN) consists of painful attacks often triggered with general activities, which cause impairment and disability. The first line of treatment consists of pharmacotherapy. However, the occurrence of many side-effects limits its application. Acute pain relief is crucial for titrating oral drugs and making time for neurosurgical intervention. This study aimed to examine the long-term anesthetic effect of QX-314 and capsaicin in trigeminal neuralgia using an animal model. TN was stimulated by surgical constriction of the infraorbital nerve in rats. After seven days, anesthesia infiltration was done, and the duration of mechanical allodynia was compared. Thirty-five male Wistar rats were randomly divided into seven groups as follows: control (normal saline); lidocaine (2%); QX314 (30 mM); lidocaine (2%)+QX314 (15 mM); lidocaine (2%)+QX314 (22 mM); lidocaine (2%)+QX314 (30 mM); and lidocaine (2%)+QX314 (30 mM) +capsaicin (1μg). QX314 in combination with lidocaine significantly increased the duration of anesthesia, which was dose-dependent. The combination of lidocaine+QX314+capsaicin could significantly increase the duration of anesthesia in trigeminal neuralgia. In the present study, we demonstrated that the combination of QX-314 with lidocaine and capsaicin produced a long-lasting, reversible local anesthesia and was superior to lidocaine alone in the fields of the duration of trigeminal neuropathic pain blockage.

Keywords: trigeminal neuralgia, capsaicin, lidocaine, long-lasting

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589 An Investigation on Students’ Reticence in Iranian University EFL Classrooms

Authors: Azizeh Chalak, Firouzeh Baktash

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Reticence is a prominent and complex phenomenon which occurs in foreign language classrooms and influences students’ oral passivity. The present study investigated the extent in which students experience reticence in the EFL classrooms and explored the underlying factors triggering reticence. The participants were 104 Iranian freshmen undergraduate male and female EFL students, who enrolled in listening and speaking courses, all majoring in English studying at Islamic Azad University Isfahan (Khorasgan) Branch and University of Isfahan, Isfahan, Iran. To collect the data, the Reticence Scale-12 (RS-12) questionnaire which measures the level of reticence consisting of six dimensions (anxiety, knowledge, timing, organization, skills, and memory) was administered to the participants. The statistical analyses showed that the reticent level was high among the Iranian EFL undergraduate students, and their major problems were feelings of anxiety and delivery skills. Moreover, the results revealed that factors such as low English proficiency, the teaching method, and lack of confidence contributed to the students’ reticence in Iranian EFL classrooms. It can be implied that language teachers’ awareness of learners’ reticence can help them choose more appropriate activities and provide a friendly environment enhancing hopefully more effective participation of EFL learners. The findings can have implications for EFL teachers, learners and policy makers.

Keywords: anxiety, Iranian EFL learners, reticence, reticence scale-12

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588 Numerical Study Pile Installation Disturbance Zone Effects on Excess Pore Pressure Dissipation

Authors: Kang Liu, Meng Liu, Meng-Long Wu, Da-Chang Yue, Hong-Yi Pan

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The soil setup is an important factor affecting pile bearing capacity; there are many factors that influence it, all of which are closely related to pile construction disturbances. During pile installation in soil, a significant amount of excess pore pressure is generated, creating disturbance zones around the pile. The dissipation rate of excess pore pressure is an important factor influencing the pile setup. The paper aims to examine how alterations in parameters within disturbance zones affect the dissipation of excess pore pressure. An axisymmetric FE model is used to simulate pile installation in clay, subsequently consolidation using Plaxis 3D. The influence of disturbed zone on setup is verified, by comparing the parametric studies in uniform field and non-uniform field. Three types of consolidation are employed: consolidation in three directions, vertical consolidation, horizontal consolidation. The results of the parametric study show that the permeability coefficient decreases, soil stiffness decreases, and reference pressure increases in the disturbance zone, resulting in an increase in the dissipation time of excess pore pressure and exhibiting a noticeable threshold phenomenon, which has been commonly overlooked in previous literature. The research in this paper suggests that significant thresholds occur when the coefficient of permeability decreases to half of the original site's value for three-directional and horizontal consolidation within the disturbed zone. Similarly, the threshold for vertical consolidation is observed when the coefficient of permeability decreases to one-fourth of the original site's value. Especially in pile setup research, consolidation is assumed to be horizontal; the study findings suggest that horizontal consolidation has experienced notable alterations as a result of the presence of disturbed zones. Furthermore, the selection of pile installation methods proves to be critical. A nonlinearity excess pore pressure formula is proposed based on cavity expansion theory, which includes the distribution of soil profile modulus with depth.

Keywords: pile setup, threshold value effect, installation effects, uniform field, non-uniform field

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587 Repeated Dose 28-Day Oral Toxicity Study Offungicides: Propinèbe, Propiconazole, And Their Mixture in Wistar Rats

Authors: Aiche Mohamed Amine, Mallem Leila, Yahia El Khansa, Boulakoud Mohamed Salah

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Until recently, toxicological studies focused on the effects of individual chemicals. However, humans and wildlife are exposed to a complex milieu of chemicals from different sources including food and water, personal care products and the environment. The aim of this study is to detect the toxicity of two fungicides and their mixtures in the fertility and oxidative damge induced in the rat. The male of rats (28) were used, they were divided in four groups (7 rats of each group) and one group was used as control. Rats were dosed orally with Propiconazole 60mg/Kg/day, Propinebe 100mg/Kg/day and their mixture 30mg Propiconazole/kg/day + 50mg Propineb/kg/day for 4 weeks. Animals were observed for clinical toxicity. At the end of treatment period, animals of all groups were scarified, blood was collected for hematological and biochemical’s analysis and desired organs were removed and weighted. The results indicated that the fungicide and their mixture were toxic in the treated animals. The semen study showed a decrease in the count and mobility of spermatozoa in all treated group, it was also a decrease in the weight of the testis and epidydimis in the treated group as compared with control. Reduced glutathione (GSH), Glutathione peroxidase (GPx) level was decreased in all treated groups.

Keywords: fungicides, mixtures, fertility, oxidative stress

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586 Students’ Perceptions of Formative Assessment Feedback: A Case Study for Undergraduate Students in Bahrain

Authors: Hasan Husain Ali Abdulnabi

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Formative assessment feedback is increasingly practiced in higher education. Instructors allocate great time and effort to provide assessment feedback. However, educators are not sure about students’ perceptions, understanding and respond to the feedback given, as very limited research have been done about what students do with feedback and whether if they understand it. This study aims to explore students’ conceptions and perceptions of formative assessment feedback through questionnaire and focus group interviews. One hundred eighty undergraduate students doing different courses filled the questionnaire, and ten focus group discussions were conducted. Basic descriptive and content analyses were used to analyze students’ responses to the questionnaire, while grounded theory with open coding was used to analyze the focus group interviews. The study revealed that most students believe assessment feedback is helpful to improve their academic performance, and they take time to read, think and discuss their feedback. Also, the study shows most students understand the feedback given. However, students expressed that most of the written feedback given are too general, and they prefer individual oral feedback as it can lead to better understanding on how what and where to improve. The study concluded that students believe formative assessment feedback is valuable, students have reasonable understanding and respond to the feedback provided. However, this practice could be improved by requesting lecturers to make more specific feedback and communicate with students on the way of interpreting and using assessment feedback as a part of the learning and teaching process.

Keywords: assessment, feedback, formative, undergraduate, higher education

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585 Information Technology and the Challenges Facing the Legal Profession in Nigeria

Authors: Odoh Ben Uruchi

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Information Technology is an outcome of the nexus between the computer technology and the communication technology which has grown as silver fiber in Nigeria. Information Technology represents the fourth generation of human communication after sight, oral and written communications. The internet, as with all path-breaking technological developments gives us all the ample privileges to act as a global community; advertise and operate across all frontiers; over boarders and beyond the control of any government. The security concerns, computer abuse and the side effects of this technology have moved to the forefront of the consciousness of law enforcement agencies. Unfortunately, Nigeria is one of the very few countries in the world to have not legislated Cyber Laws, although several unsuccessful attempts have been made in recent times at providing the legal framework for regulating the activities in Nigerian cyberspace. Traditional legal systems have led to great difficulty in keeping pace with the rapid growth of the internet and its impact throughout Nigeria. The only existing legal frameworks are constantly being challenged by technological advancement. This has created a need to constantly update and adapt the way in which we organize ourselves as Legal Practitioners in order to maintain overall control of its domestic and national interests. This paper seeks to appraise the challenges facing the legal profession in Nigeria because of want of Cyber Laws. In doing this, the paper shall highlight the loopholes in the existing laws and recommends the way forward.

Keywords: information technology, challenges, legal profession, Nigeria

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584 Drug Reaction with Eosinophilia and Systemic Symptoms (Dress) Syndrome Presenting as Multi-Organ Failure

Authors: Keshari Shrestha, Philip Vatterott

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Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal drug-related syndrome. DRESS classically presents with a diffuse maculopapular rash, fevers, and eosinophilia more than three weeks after drug exposure. DRESS can present with multi-organ involvement, with liver damage being the most common and severe. Pulmonary involvement is a less common manifestation and is associated with poor clinical outcomes. Chest imaging is often nonspecific, and symptoms can range from mild cough to acute respiratory distress syndrome (ARDS) . This is a case of a 49-year-old female with a history of recent clostridium difficile colitis status post treatment with oral vancomycin who presented with rash, acute liver and kidney failure, as well as diffuse nodular alveolar lung opacities concerning for DRESS syndrome with multi-organ involvement. Clinical Course: This patient initially presented to an outside hospital with clostridium difficile colitis, acute liver injury, and acute kidney injury. She developed a desquamating maculopapular rash in the setting of recent oral vancomycin, meloxicam, and furosemide initiation. She was hospitalized on two additional occasions with worsening altered mental status, liver injury, and acute kidney injury and was initiated on intermittent hemodialysis. Notably, she was found to have systemic eosinophilia (4100 cells/microliter) several weeks prior. She was transferred to this institution for further management where she was found to have encephalopathy, jaundice, lower extremity edema, and diffuse bilateral rhonchorous breath sounds on pulmonary examination. The patient was started on methylprednisolone for suspected DRESS syndrome. She underwent an evaluation for alternative causes of her organ failure. Her workup included a negative infectious, autoimmune, metabolic, toxic, and malignant work-up. Abdominal computed tomography (CT) and ultrasound were remarkable for evidence of hepatic steatosis and possible cirrhotic morphology. Additionally, a chest CT demonstrated diffuse and symmetric nodular alveolar lung opacities with peripheral sparing not consistent with acute respiratory distress syndrome or edema. Ultimately, her condition continued to decline, and she required intubation on several occasions. On hospital day 25 she succumbed to distributive shock in the setting of probable sepsis and multi-organ failure. Discussion: DRESS syndrome occurs in 1 in 1,000 to 10,000 patients with a mortality rate of around 10%. Anti-convulsant, anti-bacterial, anti-viral, and sulfonamide drugs are the most common drugs implicated in the development of DRESS syndrome; however, the list of offending agents is extensive . The diagnosis of DRESS syndrome is made after excluding other causes of disease such as infectious and autoimmune etiologies. The RegiSCAR scoring system is used to diagnose DRESS syndrome with 2-3 points indicating possible disease, 4-5 probable disease, and >5 definite disease. This patient scored a 7 on the RegiSCAR scale for eosinophilia, rash, organ involvement, and exclusion of other causes (infectious and autoimmune). While the pharmacologic trigger in this case is unknown, it is speculated to be caused by vancomycin, meloxicam, or furosemide due to the favorable timeline of initiation. Despite aggressive treatment, DRESS syndrome can often be fatal. Because of this, early diagnosis and treatment of patients with suspected DRESS syndrome is imperative.

Keywords: drug reaction with eosinophilia and systemic symptoms, multi-organ failure, pulmonary involvement, renal failure

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583 A Validated UPLC-MS/MS Assay Using Negative Ionization Mode for High-Throughput Determination of Pomalidomide in Rat Plasma

Authors: Muzaffar Iqbal, Essam Ezzeldin, Khalid A. Al-Rashood

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Pomalidomide is a second generation oral immunomodulatory agent, being used for the treatment of multiple myeloma in patients with disease refractory to lenalidomide and bortezomib. In this study, a sensitive UPLC-MS/MS assay was developed and validated for high-throughput determination of pomalidomide in rat plasma using celecoxib as an internal standard (IS). Liquid liquid extraction using dichloromethane as extracting agent was employed to extract pomalidomide and IS from 200 µL of plasma. Chromatographic separation was carried on Acquity BEHTM C18 column (50 × 2.1 mm, 1.7 µm) using an isocratic mobile phase of acetonitrile:10 mM ammonium acetate (80:20, v/v), at a flow rate of 0.250 mL/min. Both pomalidomide and IS were eluted at 0.66 ± 0.03 and 0.80 ± 0.03 min, respectively with a total run time of 1.5 min only. Detection was performed on a triple quadrupole tandem mass spectrometer using electrospray ionization in negative mode. The precursor to product ion transitions of m/z 272.01 → 160.89 for pomalidomide and m/z 380.08 → 316.01 for IS were used to quantify them respectively, using multiple reaction monitoring mode. The developed method was validated according to regulatory guideline for bioanalytical method validation. The linearity in plasma sample was achieved in the concentration range of 0.47–400 ng/mL (r2 ≥ 0.997). The intra and inter-day precision values were ≤ 11.1% (RSD, %) whereas accuracy values ranged from - 6.8 – 8.5% (RE, %). In addition, other validation results were within the acceptance criteria and the method was successfully applied in a pharmacokinetic study of pomalidomide in rats.

Keywords: pomalidomide, pharmacokinetics, LC-MS/MS, celecoxib

Procedia PDF Downloads 391